FDA approves Casgevy for children as young as 2 with sickle cell disease and beta thalassemia

Casgevy is the first CRISPR-based gene-editing therapy approved for children this young with either condition. HCPLive reported the FDA granted the supplemental approval 53 days after filing under its Commissioner's National Priority Voucher pilot and that it was the eighth therapy selected under that program.

Casgevy is a one-time intravenous infusion of the patient's own blood stem cells, edited outside the body to reactivate fetal hemoglobin, given after myeloablative conditioning with busulfan. Vertex Pharmaceuticals developed it with CRISPR Therapeutics.

Why treating at age 2 matters

Sickle cell disease damages organs from early childhood. Sickled cells obstruct small blood vessels and cause vaso-occlusive crises, and cumulative damage includes stroke, acute chest syndrome, renal failure and cardiopulmonary complications, according to BioPharm International. Stroke risk can begin as early as age two and increases sharply through the teenage years.

Dr Haydar Frangoul, director of the pediatric stem cell transplant program at Sarah Cannon Research Institute and TriStar Centennial Children's Hospital, told HCPLive that earlier access may let clinicians intervene before permanent organ damage develops. "The striking part is that children did extremely well, which we expect them to because they don't have end organ damage," he said.

Dr Megha Kaushal, acting deputy director of the Office of Therapeutic Products at the FDA's Center for Biologics Evaluation and Research, said in the FDA's announcement that the disorders affect growth, development and long-term health. She said making the therapy available to younger patients "opens a critical window for intervention."

The pediatric evidence is small

The pediatric data come from small trials. In sickle cell disease, 11 children aged 5 to under 12 were enrolled, and all 8 efficacy-evaluable patients met the primary endpoint. That endpoint was freedom from protocol-defined severe vaso-occlusive crises for at least 12 consecutive months within the first 24 months after infusion.

In the corresponding transfusion-dependent beta thalassemia trial in the same age group, 15 children were enrolled and 9 were efficacy-evaluable. Eight of the nine reached transfusion independence for at least 12 consecutive months, with a median duration of 20.1 months.

The FDA extended the indication to children aged 2 to under 5 by extrapolation from the 5 to under 12 data, not from direct evidence in the younger group. The pediatric results build on the CLIMB SCD-121 trial in patients aged 12 to 35. In that study, 29 of 30 efficacy-evaluable participants, or 97%, stayed free of vaso-occlusive crises for at least 12 consecutive months.

The most common adverse events in both indications were mucositis and febrile neutropenia, and decreased appetite was also reported in sickle cell patients.

Access and delivery

Vertex estimates about 5,500 additional American children are now eligible. Sickle cell disease affects an estimated 100,000 Americans. It occurs in about 1 in every 365 Black or African American births, according to the Centers for Disease Control and Prevention.

Casgevy requires collecting the patient's own blood stem cells, editing them in a laboratory, clearing the bone marrow with chemotherapy and reinfusing the edited cells. The advantage over bone marrow transplant is that no donor is required. Frangoul told WKRN that about 80% of patients do not have a family member who is a match.

TriStar Centennial Children's Hospital in Nashville now offers the treatment, and Frangoul called it a huge medical milestone. Casgevy carries a list price of approximately $2.2 million per patient, MedicalDaily reported.

What remains uncertain

The pediatric cohorts were small. The extension to children aged 2 to under 5 rests on extrapolation rather than direct trial evidence in that age group. The label covers sickle cell disease with recurrent vaso-occlusive crises and transfusion-dependent beta thalassemia, not every patient with either diagnosis.

Patients are planned to be followed for up to 15 years after infusion, according to the prescribing information cited by HCPLive. Frangoul told HCPLive he hopes the pediatric approval "won't be the last milestone in the field."